scholarly journals Critical role of Frizzled1 in age-related alterations of Wnt/β-catenin signal in myogenic cells during differentiation

2014 ◽  
Vol 19 (4) ◽  
pp. 287-296 ◽  
Author(s):  
Ryosuke Doi ◽  
Mitsuharu Endo ◽  
Kimi Yamakoshi ◽  
Yuji Yamanashi ◽  
Michiru Nishita ◽  
...  
Keyword(s):  
Critical Role ◽  
Myogenic Cells ◽  
Age Related

Pathogenesis of Age-related Cataract: a systematic review of proteomic studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Christina Karakosta ◽  
Argyrios Tzamalis ◽  
Michalis Aivaliotis ◽  
Ioannis Tsinopoulos
Keyword(s):  
Systematic Review ◽  
Oxidant Stress ◽  
Critical Role ◽  
Human Lens ◽  
Nuclear Cataract ◽  
Cataract Formation ◽  
Post Translational Modification ◽  
Ability To Act ◽  
Age Related

Background/Objective:: The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens. Materials and Methods:: We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses. Results:: Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7. Conclusion:: D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in human, while the role of oxidant stress in age-related cataract formation is dominant.

scholarly journals Critical role of the CD44lowCD62Llow CD8+ T cell subset in restoring antitumor immunity in aged mice

2021 ◽  
Vol 118 (23) ◽  
pp. e2103730118
Author(s):  
Yuka Nakajima ◽  
Kenji Chamoto ◽  
Takuma Oura ◽  
Tasuku Honjo
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Critical Role ◽  
Cell Subset ◽  
Effector Memory ◽  
T Cell Subset ◽  
Aged Mice ◽  
Age Related

CD8+ T cells play a central role in antitumor immune responses that kill cancer cells directly. In aged individuals, CD8+ T cell immunity is strongly suppressed, which is associated with cancer and other age-related diseases. The mechanism underlying this age-related decrease in immune function remains largely unknown. This study investigated the role of T cell function in age-related unresponsiveness to PD-1 blockade cancer therapy. We found inefficient generation of CD44lowCD62Llow CD8+ T cell subset (P4) in draining lymph nodes of tumor-bearing aged mice. In vitro stimulation of naive CD8+ T cells first generated P4 cells, followed by effector/memory T cells. The P4 cells contained a unique set of genes related to enzymes involved in one-carbon (1C) metabolism, which is critical to antigen-specific T cell activation and mitochondrial function. Consistent with this finding, 1C-metabolism–related gene expression and mitochondrial respiration were down-regulated in aged CD8+ T cells compared with young CD8+ T cells. In aged OVA-specific T cell receptor (TCR) transgenic mice, ZAP-70 was not activated, even after inoculation with OVA-expressing tumor cells. The attenuation of TCR signaling appeared to be due to elevated expression of CD45RB phosphatase in aged CD8+ T cells. Surprisingly, strong stimulation by nonself cell injection into aged PD-1–deficient mice restored normal levels of CD45RB and ameliorated the emergence of P4 cells and 1C metabolic enzyme expression in CD8+ T cells, and antitumor activity. These findings indicate that impaired induction of the P4 subset may be responsible for the age-related resistance to PD-1 blockade, which can be rescued by strong TCR stimulation.

scholarly journals Role of the Undergraduate Student Research Assistant in the New Millennium

2004 ◽  
Vol 3 (4) ◽  
pp. 235-240 ◽  
Author(s):  
Thais Dutra Nascimento Silva ◽  
Lúcia Cristina da Cunha Aguiar ◽  
Jaqueline Leta ◽  
Dilvani Oliveira Santos ◽  
Fernanda Serpa Cardoso ◽  
...  
Keyword(s):  
Undergraduate Students ◽  
Undergraduate Student ◽  
Critical Role ◽  
Academic Research ◽  
Scientific Data ◽  
Research Assistant ◽  
Age Related ◽  
Research Careers ◽  
New Research

In this study, we analyze the contribution of the undergraduate student who participates in the process of generating scientific data and developing a research project using Brazilian research as an example. Historically, undergraduate students have performed the critical role of research assistants in developing countries. This aspect has been underappreciated as a means of generating scientific data in Brazilian research facilities. Brazilian educational institutions are facing major age-related generational changes among the science faculty within the next 5–10 yr. A lack of adequate support for graduate students leads to a concern that undergraduates will not be interested in choosing research assistant programs and, subsequently, academic research careers. To remedy this situation it is important to focus on ways to encourage new research careers and enhance university–industry collaborations.

scholarly journals Nrf2 activation induces mitophagy and reverses Parkin/Pink1 knock down-mediated neuronal and muscle degeneration phenotypes

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Sentiljana Gumeni ◽  
Eleni-Dimitra Papanagnou ◽  
Maria S. Manola ◽  
Ioannis P. Trougakos
Keyword(s):  
Critical Role ◽  
Model Organism ◽  
Dependent Manner ◽  
Degenerative Diseases ◽  
Knock Down ◽  
Age Related ◽  
Degenerative Disorders ◽  
Pathway Activation

AbstractThe balanced functionality of cellular proteostatic modules is central to both proteome stability and mitochondrial physiology; thus, the age-related decline of proteostasis also triggers mitochondrial dysfunction, which marks multiple degenerative disorders. Non-functional mitochondria are removed by mitophagy, including Parkin/Pink1-mediated mitophagy. A common feature of neuronal or muscle degenerative diseases, is the accumulation of damaged mitochondria due to disrupted mitophagy rates. Here, we exploit Drosophila as a model organism to investigate the functional role of Parkin/Pink1 in regulating mitophagy and proteostatic responses, as well as in suppressing degenerative phenotypes at the whole organism level. We found that Parkin or Pink1 knock down in young flies modulated proteostatic components in a tissue-dependent manner, increased cell oxidative load, and suppressed mitophagy in neuronal and muscle tissues, causing mitochondrial aggregation and neuromuscular degeneration. Concomitant to Parkin or Pink1 knock down cncC/Nrf2 overexpression, induced the proteostasis network, suppressed oxidative stress, restored mitochondrial function, and elevated mitophagy rates in flies’ tissues; it also, largely rescued Parkin or Pink1 knock down-mediated neuromuscular degenerative phenotypes. Our in vivo findings highlight the critical role of the Parkin/Pink1 pathway in mitophagy, and support the therapeutic potency of Nrf2 (a druggable pathway) activation in age-related degenerative diseases.

scholarly journals Can diagnostic imaging help improve elder abuse detection?

2020 ◽  
Vol 93 (1110) ◽  
pp. 20190632
Author(s):  
Taryn J Rohringer ◽  
Tony E Rosen ◽  
Mihan R Lee ◽  
Pallavi Sagar ◽  
Kieran J Murphy
Keyword(s):  
Diagnostic Imaging ◽  
Elder Abuse ◽  
Current Knowledge ◽  
Critical Role ◽  
Systematic Research ◽  
Imaging Findings ◽  
Clinical Workflow ◽  
Age Related ◽  
Patterns Of Injury

Elder abuse is an underdetected, under-reported issue with severe consequences. Its detection presents unique challenges based on characteristics of this vulnerable population, including cognitive impairment, age-related deconditioning, and an increased number of co-morbidities, all of which predispose to increase vulnerability to injury. While radiologists play a critical role in detection of child abuse, this role is currently not paralleled in detection of elder abuse. We conducted a thorough review of the literature using MEDLINE to describe the current knowledge on injury patterns and injury findings seen in elder abuse, as well as barriers to and recommendations for an increased role of diagnostic imaging in elder abuse detection. Barriers limiting the role of radiologists include lack of training and paucity of rigorous systematic research delineating distinctive imaging findings for physical elder abuse. We outline the current ways in which imaging can help raise clinical suspicion for elder abuse, including inconsistencies between purported mechanism of injury and imaging findings, injury location, multiple injuries at differing stages of healing, and particular patterns of injury likely to be intentionally inflicted. We additionally outline the mechanism by which medical education and clinical workflow may be modified to increase the role for imaging and radiologist participation in detecting abuse in older adult patients, and identify potential future directions for further systematic research.

scholarly journals Inhibition of JAK-STAT Signaling Pathway Alleviates Age-Related Phenotypes in Tendon Stem/Progenitor Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Minhao Chen ◽  
Longfei Xiao ◽  
Guangchun Dai ◽  
Panpan Lu ◽  
Yuanwei Zhang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Signaling Pathway ◽  
Critical Role ◽  
Vital Role ◽  
Actin Dynamics ◽  
Tendon Tissue ◽  
Age Related ◽  
Stat Signaling ◽  
Secretory Phenotype

Diminished regeneration or healing capacity of tendon occurs during aging. It has been well demonstrated that tendon stem/progenitor cells (TSPCs) play a vital role in tendon maintenance and repair. Here, we identified an accumulation of senescent TSPCs in tendon tissue with aging. In aged TSPCs, the activity of JAK-STAT signaling pathway was increased. Besides, genetic knockdown of JAK2 or STAT3 significantly attenuated TSPC senescence in aged TSPCs. Pharmacological inhibition of JAK-STAT signaling pathway with AG490 similarly attenuated cellular senescence and senescence-associated secretory phenotype (SASP) of aged TSPCs. In addition, inhibition of JAK-STAT signaling pathway also restored the age-related dysfunctions of TSPCs, including self-renewal, migration, actin dynamics, and stemness. Together, our findings reveal the critical role of JAK-STAT signaling pathway in the regulation of TSPC aging and suggest an ideal therapeutic target for the age-related tendon disorders.

Up-Regulation of GATA4 Regulates Human Lens Epithelial Cell Function in Age-Related Cataract

2020 ◽  
Vol 63 (6) ◽  
pp. 564-571
Author(s):  
Xiaodong Xie ◽  
Xiaofei Song ◽  
Xin Liu ◽  
Xiaogang Luo ◽  
Maidina Nabijiang ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Cell Function ◽  
Critical Role ◽  
Lens Epithelial Cell ◽  
Human Lens ◽  
Dependent Manner ◽  
Age Related

<b><i>Purpose:</i></b> GATA4 has emerged as a novel regulator that plays a critical role in mediating senescence. However, the role of GATA4 in age-related cataract (ARC), the leading cause of visual impairment, requires further elucidation. <b><i>Methods:</i></b> GATA4 expression was measured by quantitative RT-PCR and capillary Western immunoassay (WES). The MTT assay, EdU assay, and rhodamine-123/Hoechst and calcein-AM/propidium iodide double staining were used to investigate the role of GATA4 in the viability, proliferation, and apoptosis of cultured human lens epithelial cells (HLECs). <b><i>Results:</i></b> HLECs were subjected to 3 different treatment models, including prolonged exposure to low-dose H<sub>2</sub>O<sub>2</sub>, UVB irradiation, and mild heating, to simulate senescence and apoptosis. GATA4 expression was significantly increased in these models in a time- and dose-dependent manner. Overexpression of GATA4 reduced cell viability, accelerated apoptosis development, and reduced the proliferation of HLECs. Furthermore, the expression of GATA4 from ARC was up-regulated at both mRNA and at protein level compared with clear lenses. <b><i>Conclusion:</i></b> GATA4 is up-regulated in all 3 models of HLECs in vitro and the cells from ARC lenses in vivo. Up-regulation of GATA4 mediates HLEC dysfunction. GATA4-mediated effects in HLECs would provide a novel insight into the pathogenesis of ARC.

scholarly journals Cataract in the human lens: a systematic review of proteomic studies

2019 ◽  
Author(s):  
Christina Karakosta ◽  
Argyrios Tzamalis ◽  
Michalis Aivaliotis ◽  
Ioannis Tsinopoulos
Keyword(s):  
Systematic Review ◽  
Oxidant Stress ◽  
Critical Role ◽  
Human Lens ◽  
Cataract Formation ◽  
Post Translational Modification ◽  
Lens Crystallins ◽  
Ability To Act ◽  
Age Related

AbstractBackground/AimThe aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens.MethodsWe searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses.ResultsDeamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7.ConclusionD-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in man, while the role of oxidant stress in age-related cataract formation is dominant.SynopsisThe oxidative stress and the post-translational modification of deamidation in lens crystallins seem to play a significant role in the formation of age-related cataract in human.

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